At the present time there is no specific treatment for human acute pancreatitis. Exogenously administered secretin given concomitantly with ceruletide (an acute pancreatitis inducing agent) has been shown to exert a striking protective effect on induction of the pathological process. The goal of this project is to evaluate the efficacy and safety of intravenously administered secretin in amelioration of established ceruletide induced acute pancreatitis in rats and dogs in an effort to provide a specific form of treatment for human acute pancreatitis. Specific aims in this study are first to establish the efficacy, safety and the optimal dose of intravenous secretin to ameliorate acute ceruletide induced pancreatitis in unconscious, pancreatic duct cannulated rats and also to determine whether this hormone can consistently reestablish normal pancreatic juice flow and protein output. Subsequently in conscious rat and dog models using prior, optimally established doses of secretin we will evaluate the ameliorative effect of this hormone on established ceruletide induced acute pancreatitis. Serum levels of lipase, amylase and trypsinogen and macroscopic, microscopic and ultrastructural changes in the pancreas will be used as markers for establishing the efficacy of the ameliorative process. This program is clearly directed toward development of a possible mode of therapy for acute pancreatitis in two animal species. Should our hypothesis that secretin therapy may ameliorate induced acute pancreatitis be proven, then extension of this work to assessment of the role of this hormone in human acute pancreatitis would appear reasonable. Any form of therapy that might ameliorate the severity of this disease in humans would be a very welcome addition to our presently limited therapeutic armamentarium.